rs7336489

Variant names:

• chr13-59699164-C-T
• rs7336489
• NM_001042517.2:c.3320-32318G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400324.9(DIAPH3):​c.3320-32318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,134 control chromosomes in the GnomAD database, including 2,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2165 hom., cov: 32)
• Consequence: DIAPH3 ENST00000400324.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 1 publications found

Genes affected

DIAPH3 (HGNC:15480): (diaphanous related formin 3) This gene encodes a member of the diaphanous subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. Mutations in this gene are associated with autosomal dominant auditory neuropathy 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

DIAPH3 Gene-Disease associations (from GenCC):

• autosomal dominant auditory neuropathy 1

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• auditory neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400324.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	NM_001042517.2	MANE Select	c.3320-32318G>A		intron	N/A	NP_001035982.1
	DIAPH3	NM_001258366.2		c.3287-32318G>A		intron	N/A	NP_001245295.1
	DIAPH3	NM_001258367.2		c.3182-32318G>A		intron	N/A	NP_001245296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	ENST00000400324.9	TSL:1 MANE Select	c.3320-32318G>A		intron	N/A	ENSP00000383178.3
	DIAPH3	ENST00000377908.6	TSL:1	c.3287-32318G>A		intron	N/A	ENSP00000367141.2
	DIAPH3	ENST00000400320.5	TSL:1	c.3182-32318G>A		intron	N/A	ENSP00000383174.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24630 AN: 152016 Hom.: 2162 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24638 AN: 152134 Hom.: 2165 Cov.: 32 AF XY: 0.165 AC XY: 12259 AN XY: 74382

African (AFR) AF: 0.110 AC: 4575 AN: 41514

American (AMR) AF: 0.119 AC: 1826 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1458 AN: 5160

South Asian (SAS) AF: 0.182 AC: 879 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2462 AN: 10584

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11946 AN: 67982

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.167 Hom.: 3083

Bravo AF: 0.150

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0020
DANN	Benign	0.21
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7336489; hg19: chr13-60273298;